Involvement of Choline Transporter-Like Proteins, CTL1 and CTL2, in Glucocorticoid-Induced Acceleration of Phosphatidylcholine Synthesis via Increased Choline Uptake

Toshimichi Nakamura; Ryohei Fujiwara; Naoki Ishiguro; Masanobu Oyabu; Takeo Nakanishi; Yoshiyuki Shirasaka; Tomoji Maeda; Ikumi Tamai

doi:10.1248/bpb.33.691

Regular Articles

Involvement of Choline Transporter-Like Proteins, CTL1 and CTL2, in Glucocorticoid-Induced Acceleration of Phosphatidylcholine Synthesis via Increased Choline Uptake

Toshimichi Nakamura, Ryohei Fujiwara, Naoki Ishiguro, Masanobu Oyabu, Takeo Nakanishi, Yoshiyuki Shirasaka, Tomoji Maeda, Ikumi Tamai

Author information

Toshimichi Nakamura
Department of Membrane Transport and Pharmacokinetics, Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University
Faculty of Pharmaceutical Sciences, Tokyo University of Science
Ryohei Fujiwara
Faculty of Pharmaceutical Sciences, Tokyo University of Science
Naoki Ishiguro
Faculty of Pharmaceutical Sciences, Tokyo University of Science
Masanobu Oyabu
Faculty of Pharmaceutical Sciences, Tokyo University of Science
Takeo Nakanishi
Department of Membrane Transport and Pharmacokinetics, Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University
Yoshiyuki Shirasaka
Department of Membrane Transport and Pharmacokinetics, Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University
Faculty of Pharmaceutical Sciences, Tokyo University of Science
Tomoji Maeda
Department of Membrane Transport and Pharmacokinetics, Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University
Department of Neuroscience, Faculty of Pharmaceutical Sciences, Iwate Medical University
Ikumi Tamai
Department of Membrane Transport and Pharmacokinetics, Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University
Faculty of Pharmaceutical Sciences, Tokyo University of Science

Keywords: choline transporter, alveolar type II cell, dexamethasone, glucocorticoid receptor, lung surfactant

JOURNAL FREE ACCESS

2010 Volume 33 Issue 4 Pages 691-696

DOI https://doi.org/10.1248/bpb.33.691

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Abstract

Phosphatidylcholine (PC) production is accelerated by glucocorticoid, such as dexamethasone (DEX), which enhances fetal lung maturation, promotes differentiation of alveolar type II (ATII) cells, and increases production of both lipid and protein components of lung surfactant. We previously demonstrated that inhibition of choline uptake by ATII cells leads to a decrease of PC synthesis. Since choline uptake may play a critical role in PC production and lung surfactant homeostasis for normal breathing, it is of interest to characterize transporters controlling the disposition of choline in ATII cells. Therefore, we studied the gene regulation and activity of choline transporters in A549 cells, a human ATII cell line. A549 cells were exposed to DEX for 24 h, and mRNA expression levels of choline transporters-like protein 1, (CTL1) and CTL2, were measured using real-time reverse transcription polymerase chain reaction. CTL1 and CTL2 mRNAs were strongly induced by DEX treatment of A549 cells, and the DEX-treated cells showed a significant increase in initial uptake rate of [³H]choline, which was assessed under ATP-depleted conditions to block the influence of consumption of choline by choline kinase. Transfection of A549 cells with either CTL1- or CTL2-small interfering RNAs significantly decreased [³H]choline uptake. In conclusion, choline transport in A549 cells is increased by treatment with DEX, and the increase is mediated by induction of functional choline transporters CTL1 and CTL2.

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